AzTrials
AzTrials

Breast CancerPhase 3NCT00041119

Four Versus Six Cycles of Cyclophosphamide/Doxorubicin or Paclitaxel in Adjuvant Breast Cancer

A Phase 3 study testing AC regimen, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by Alliance for Clinical Trials in Oncology at 527 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This randomized phase III trial studies cyclophosphamide and doxorubicin hydrochloride compared with paclitaxel as adjuvant therapy in treating breast cancer in women with 0-3 positive axillary lymph nodes. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
AC regimen, cyclophosphamide and doxorubicin hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,871 participants
Where
527 sitesin 2 countries
Study dates
May 2002to Jun 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Eligibility Criteria:

  • Patients must have histologically confirmed invasive carcinoma of the female breast, with 0-3 positive axillary lymph nodes
  • Patients must have 0-3 positive axillary lymph nodes to be eligible for this study; patients with node-negative breast cancer should have sufficiently "high risk" disease to warrant chemotherapy; as general guidelines, node-negative patients with tumors of >= 1 cm or estrogen or progesterone receptor negative tumors of any size may be eligible; ultimately though, the definition of "high risk" may be determined by the treating physician, and if the treating physician feels the patient warrants chemotherapy, the patient is eligible; for patients with 1-3 positive axillary nodes, the patient is eligible regardless of primary breast tumor characteristics, if in the opinion of the treating physician, chemotherapy is deemed potentially beneficial to the patient
  • If the patient has had a negative sentinel node biopsy, then no further axillary dissection is required, and the patient is determined to be node-negative; if an axillary dissection, without a sentinel node biopsy, is performed to determine nodal status, at least six axillary lymph nodes must be removed and analyzed and negative for the patient to be considered node-negative; axillary nodes with single cells or tumor clusters =< 0.2 mm by either hematoxylin and eosin stain (H\&E) or immunohistochemistry (IHC), will be considered node-negative; lymph nodes positive for polymerase chain reaction (PCR) with tumor cells/clusters =< 0.2 mm will be considered node-negative; any axillary lymph node with tumor clusters > 0.2 mm will be considered positive
  • If the patient has a sentinel node biopsy and one of the sentinel nodes is positive, as defined by tumor clusters > 0.2 mm, an axillary dissection must be performed; a total of at least 6 axillary lymph nodes, including sentinel nodes plus the subsequent dissection, must be removed for the patient to be eligible; of all the lymph nodes removed from both the sentinel node procedure and the axillary dissection, 1-3 must be positive for the patient to be eligible as a node-positive patient; if an axillary dissection is done without a sentinel node procedure, at least 6 lymph nodes must be removed and a 1-3 nodes must be positive for the patient to be considered node-positive and eligible for this study
  • Determination of involvement of axillary nodes with metastatic cancer will follow the revised tumor-node-metastasis (TNM) staging system: axillary nodes with single cells with tumor clusters =< 0.2 mm, by either H\&E or immunohistochemistry (IHC), will be considered negative axillary node; lymph nodes positive for PCR with tumor cells/clusters < 0.2 mm will be considered negative axillary node; any axillary lymph node with clusters > 0.2 mm will be considered to be positive
  • Patients with estrogen-receptor and/or progesterone receptor negative, positive, or unknown tumors are eligible; estrogen-receptor (ER) and progesterone receptor (PgR) assays should be performed by immunohistochemical methods according to the local institution's standard protocol
  • Patients with human epidermal growth factor receptor 2 (HER2) positive, negative or unknown disease are eligible for this trial; patients whose tumors are HER2 positive by either immunohistochemistry 3+ staining or demonstrate gene amplification by fluorescence in situ hybridization (FISH) may receive trastuzumab
  • There must be negative tumor margins for invasive cancer and ductal carcinoma in situ (DCIS) in the case of mastectomy or lumpectomy; lobular carcinoma in situ (LCIS) is acceptable at the margin
  • Patients with multi-centric breast cancer are eligible as long as all known disease is resected with negative margins, and have 0-3 positive axillary lymph nodes
  • Patients must be registered within 84 days of the last breast surgery; patients must have undergone either modified radical mastectomy or lumpectomy; for patients undergoing sentinel node sampling or axillary dissection a simple mastectomy is acceptable; lumpectomy patients must receive radiation therapy; for patients treated with radiation therapy prior to chemotherapy, the patients should be registered on this study after the conclusion of radiation, with chemotherapy administration beginning within 7 days of registration
  • All primary breast and axillary node surgery must be completed prior to enrollment on study
  • No previous trastuzumab, chemotherapy or hormonal therapy for this malignancy, except for tamoxifen therapy
  • No previous anthracycline chemotherapy for any disease
  • Patients with locally advanced breast cancer, inflammatory breast cancer or metastatic breast cancer are not eligible; patients with involvement of dermal lymphatics on pathology are not eligible, even if there are no clinical signs of inflammatory cancer
  • Patients with bilateral, synchronous invasive breast cancer are eligible as long as both primary tumors; if a patient has an invasive cancer on one side that meets the eligibility criteria, and DCIS or LCIS on the contralateral side, the patient is eligible; DCIS or LCIS should be managed according to institutional guidelines
  • Patients must be disease free from prior malignancies for > 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix; patients with a history of invasive breast cancer, or DCIS are eligible if they have been disease free for > 5 years; patients with a history of LCIS are eligible regardless of the interval from diagnosis
  • Common Toxicity Criteria (CTC) performance status 0-1
  • Women must not be pregnant or nursing
  • Concomitant exogenous hormone therapy, including oral contraceptives, post-menopausal hormone replacement therapy, and raloxifene must be stopped before patients can be enrolled
  • Patients may have received up to 4 weeks of tamoxifen therapy for this malignancy and still be eligible for this study; patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or for other indicators (e.g. osteoporosis) are eligible; tamoxifen therapy or other SERMs must be discontinued before the patient is enrolled on this study
  • The use of bisphosphonates for the treatment of osteoporosis is permitted; the use of raloxifene is not permitted are enrollment on this study
  • Patients must have adequate organ function including no active congestive heart failure, and no myocardial infarction < 6 months from time of registration
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,00/mm^3
  • Creatinine =< 2.0 mg/dl
  • Bilirubin =< 1.5 x upper limits of institutional normal
  • Patients may be enrolled on adjuvant bisphosphonate studies; patients may be enrolled concurrently or sequentially on 40101 and bisphosphonate trials
  • Patients may be enrolled on adjuvant hormonal studies approved by CALGB or Cancer Trials Support Unit (CTSU), such as the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) trials

Trial locations and contacts

527 sites in 2 countries.

301 sites in 2 countries

United States300 sites

  • Oncology Services of Aberdeen

    Aberdeen, South Dakota, 57401

  • Hickman Cancer Center at Bixby Medical Center

    Adrian, Michigan, 49221

  • Summa Center for Cancer Care at Akron City Hospital

    Akron, Ohio, 44309-2090

  • Saint Anthony's Hospital at Saint Anthony's Health Center

    Alton, Illinois, 62002

  • Harrington Cancer Center

    Amarillo, Texas, 79106

  • McFarland Clinic, PC

    Ames, Iowa, 50010

  • Saint Joseph Mercy Cancer Center

    Ann Arbor, Michigan, 48106-0995

  • CCOP - Michigan Cancer Research Consortium

    Ann Arbor, Michigan, 48106

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109-0942

  • Regional Medical Center

    Anniston, Alabama, 36202

  • Randolph Hospital

    Asheboro, North Carolina, 27203-5400

  • Cancer Resource Center at King's Daughters Medical Center

    Ashland, Kentucky, 41101-0151

  • Sturdy Memorial Hospital

    Attleboro, Massachusetts, 02703

  • Auburn Regional Center for Cancer Care

    Auburn, Washington, 98002

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • Aurora Presbyterian Hospital

    Aurora, Colorado, 80012

  • Rush-Copley Cancer Care Center

    Aurora, Illinois, 60504

  • Greenebaum Cancer Center at University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

  • CancerCare of Maine at Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Barberton Citizens Hospital

    Barberton, Ohio, 44203

  • Pennington Cancer Center at Baton Rouge General

    Baton Rouge, Louisiana, 70806

  • Mary Bird Perkins Cancer Center - Baton Rouge

    Baton Rouge, Louisiana, 70809

  • Ochsner Health Center - Bluebonnet

    Baton Rouge, Louisiana, 70809

  • St. Francis Hospital and Health Centers - Beech Grove Campus

    Beech Grove, Indiana, 46107

  • St. Joseph Cancer Center

    Bellingham, Washington, 98225

  • MeritCare Bemidji

    Bemidji, Minnesota, 56601

  • Alta Bates Summit Comprehensive Cancer Center

    Berkeley, California, 94704

  • Hematology Oncology Associates of the Quad Cities

    Bettendorf, Iowa, 52722

  • CCOP - Montana Cancer Consortium

    Billings, Montana, 59101

  • Hematology-Oncology Centers of the Northern Rockies - Billings

    Billings, Montana, 59101

  • Northern Rockies Radiation Oncology Center

    Billings, Montana, 59101

  • St. Vincent Healthcare Cancer Care Services

    Billings, Montana, 59101

  • Billings Clinic - Downtown

    Billings, Montana, 59107-7000

  • UAB Comprehensive Cancer Center

    Birmingham, Alabama, 35294

  • Bismarck Cancer Center

    Bismarck, North Dakota, 58501

  • Medcenter One Hospital Cancer Care Center

    Bismarck, North Dakota, 58501

  • Mid Dakota Clinic, PC

    Bismarck, North Dakota, 58501

  • St. Alexius Medical Center Cancer Center

    Bismarck, North Dakota, 58502

  • Mountain States Tumor Institute at St. Luke's Regional Medical Center

    Boise, Idaho, 83712

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber/Brigham and Women's Cancer Center

    Boston, Massachusetts, 02115

  • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Boulder Community Hospital

    Boulder, Colorado, 80301-9019

  • Wood County Oncology Center

    Bowling Green, Ohio, 43402

  • Bozeman Deaconess Cancer Center

    Bozeman, Montana, 59715

  • Skaggs Cancer Center at Skaggs Regional Medical Center

    Branson, Missouri, 65616

  • Olympic Hematology and Oncology

    Bremerton, Washington, 98310

  • Caritas St. Elizabeth's Medical Center

    Brighton, Massachusetts, 02135-2997

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Peninsula Medical Center

    Burlingame, California, 94010

  • Lahey Clinic Medical Center - Burlington

    Burlington, Massachusetts, 01805

  • Alamance Cancer Center at Alamance Regional Medical Center

    Burlington, North Carolina, 27216

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • St. James Healthcare Cancer Care

    Butte, Montana, 59701

  • Mercy Cancer Center at Mercy Medical Center

    Canton, Ohio, 44708

  • Aultman Cancer Center at Aultman Hospital

    Canton, Ohio, 44710-1799

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • East Bay Radiation Oncology Center

    Castro Valley, California, 94546

  • Valley Medical Oncology Consultants - Castro Valley

    Castro Valley, California, 94546

  • Iowa Blood and Cancer Care

    Cedar Rapids, Iowa, 52402

  • St. Luke's Hospital

    Cedar Rapids, Iowa, 52402

  • Cedar Rapids Oncology Associates

    Cedar Rapids, Iowa, 52403

  • Mercy Regional Cancer Center at Mercy Medical Center

    Cedar Rapids, Iowa, 52403

  • Providence Centralia Hospital

    Centralia, Washington, 98531-9027

  • Cancer Center of Kansas, PA - Chanute

    Chanute, Kansas, 66720

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7295

  • Roper St. Francis Cancer Center at Roper Hospital

    Charleston, South Carolina, 29401

  • Martha Jefferson Hospital Cancer Care Center

    Charlottesville, Virginia, 22901

  • Saint Luke's Hospital

    Chesterfield, Missouri, 63017

  • Mount Sinai Hospital Medical Center

    Chicago, Illinois, 60608

  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University

    Chicago, Illinois, 60611-3013

  • Hematology and Oncology Associates

    Chicago, Illinois, 60611

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612-7243

  • Swedish Covenant Hospital

    Chicago, Illinois, 60625

  • Creticos Cancer Center at Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Marshfield Clinic - Chippewa Center

    Chippewa Falls, Wisconsin, 54729

  • Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

  • MetroHealth Cancer Care Center at MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • North Coast Cancer Care - Clyde

    Clyde, Ohio, 43410

  • Memorial Hospital Cancer Center - Colorado Springs

    Colorado Springs, Colorado, 80909

  • Penrose Cancer Center at Penrose Hospital

    Colorado Springs, Colorado, 80933

  • Ellis Fischel Cancer Center at University of Missouri - Columbia

    Columbia, Missouri, 65203

  • Palmetto Health South Carolina Cancer Center

    Columbia, South Carolina, 29203

  • John B. Amos Cancer Center

    Columbus, Georgia, 31904

  • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210-1240

  • Riverside Methodist Hospital Cancer Care

    Columbus, Ohio, 43214-3998

  • CCOP - Columbus

    Columbus, Ohio, 43215

  • Grant Medical Center Cancer Care

    Columbus, Ohio, 43215

  • Mount Carmel Health - West Hospital

    Columbus, Ohio, 43222

  • Doctors Hospital at Ohio Health

    Columbus, Ohio, 43228

  • New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care

    Concord, New Hampshire, 03301

  • Batte Cancer Center at Northeast Medical Center

    Concord, North Carolina, 28025

  • Mercy and Unity Cancer Center at Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Heartland Oncology and Hematology

    Council Bluffs, Iowa, 51503

  • Ochsner Health Center - Covington

    Covington, Louisiana, 70433

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Genesis Regional Cancer Center at Genesis Medical Center

    Davenport, Iowa, 52803

  • Grandview Hospital

    Dayton, Ohio, 45405

  • Good Samaritan Hospital

    Dayton, Ohio, 45406

  • David L. Rike Cancer Center at Miami Valley Hospital

    Dayton, Ohio, 45409

  • Samaritan North Cancer Care Center

    Dayton, Ohio, 45415

  • CCOP - Dayton

    Dayton, Ohio, 45420

  • Herbert D. Kerman Regional Oncology Center - Daytona Beach

    Daytona Beach, Florida, 32114

  • Oakwood Cancer Center at Oakwood Hospital and Medical Center

    Dearborn, Michigan, 48123-2500

  • Decatur Memorial Hospital Cancer Care Institute

    Decatur, Illinois, 62526

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • St. Anthony Central Hospital

    Denver, Colorado, 80204

  • Porter Adventist Hospital

    Denver, Colorado, 80210

  • Presbyterian - St. Luke's Medical Center

    Denver, Colorado, 80218

  • St. Joseph Hospital

    Denver, Colorado, 80218

  • Rose Medical Center

    Denver, Colorado, 80220

  • CCOP - Colorado Cancer Research Program

    Denver, Colorado, 80224-2522

  • Mercy Capitol Hospital

    Des Moines, Iowa, 50307

  • CCOP - Iowa Oncology Research Association

    Des Moines, Iowa, 50309

  • John Stoddard Cancer Center at Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates at John Stoddard Cancer Center

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates at Mercy Cancer Center

    Des Moines, Iowa, 50314

  • Mercy Cancer Center at Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • John Stoddard Cancer Center at Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Cancer Center of Kansas, PA - Dodge City

    Dodge City, Kansas, 67801

  • Duluth Clinic Cancer Center - Duluth

    Duluth, Minnesota, 55805-1983

  • CCOP - Duluth

    Duluth, Minnesota, 55805

  • Miller - Dwan Medical Center

    Duluth, Minnesota, 55805

  • St. Luke's Hospital Cancer Care Center

    Duluth, Minnesota, 55805

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • CCOP - Hematology-Oncology Associates of Central New York

    East Syracuse, New York, 13057

  • Marshfield Clinic Cancer Care at Regional Cancer Center

    Eau Claire, Wisconsin, 54701

  • Luther Midlelfort Hospital

    Eau Claire, Wisconsin, 54702

  • Midelfort Clinic - Luther

    Eau Claire, Wisconsin, 54703-1510

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Cancer Center of Kansas, PA - El Dorado

    El Dorado, Kansas, 67042

  • Alexian Brothers Radiation Oncology

    Elk Grove Village, Illinois, 60007

  • Elkhart Clinic, LLC

    Elkhart, Indiana, 46514-2098

  • Elkhart General Hospital

    Elkhart, Indiana, 46515

  • Vince Lombardi Cancer Center at Aurora Lakeland Medical Center - Elkhorn

    Elkhorn, Wisconsin, 53121

  • Union Hospital Cancer Program at Union Hospital

    Elkton MD, Maryland, 21921

  • Elmhurst Hospital Center

    Elmhurst, New York, 11373

  • Swedish Medical Center

    Englewood, Colorado, 80110

  • St. Francis Hospital

    Evanston, Illinois, 60202

  • Center for Cancer Care at Exeter Hospital

    Exeter, New Hampshire, 03833

  • Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • Hudner Oncology Center at Saint Anne's Hospital - Fall River

    Fall River, Massachusetts, 02721

  • CCOP - MeritCare Hospital

    Fargo, North Dakota, 58122

  • MeritCare Broadway

    Fargo, North Dakota, 58122

  • Cape Fear Valley Medical Center Cancer Center

    Fayetteville, North Carolina, 28302-2000

  • St. Francis Hospital

    Federal Way, Washington, 98003

  • Fergus Falls Medical Group, PA

    Fergus Falls, Minnesota, 56537

  • Blanchard Valley Medical Associates

    Findlay, Ohio, 45840

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • McLeod Regional Medical Center

    Florence, South Carolina, 29501

  • Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital

    Fort Lauderdale, Florida, 33308

  • Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

    Fort Smith, Arkansas, 72903

  • Fort Wayne Medical Oncology and Hematology

    Fort Wayne, Indiana, 46845

  • Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Frederick Memorial Hospital Regional Cancer Therapy Center

    Frederick, Maryland, 21701

  • Fredericksburg Oncology, Incorporated

    Fredericksburg, Virginia, 22401

  • Valley Medical Oncology

    Fremont, California, 94538

  • Washington Township Hospital

    Fremont, California, 94538

  • California Cancer Center - Woodward Park Office

    Fresno, California, 93720

  • Cancer Care Associates

    Fresno, California, 93720

  • Mercy and Unity Cancer Center at Unity Hospital

    Fridley, Minnesota, 55432

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Northeast Georgia Medical Center

    Gainesville, Georgia, 30501

  • Addison Gilbert Hospital

    Gloucester, Massachusetts, 01930

  • Wayne Memorial Hospital, Incorporated

    Goldsboro, North Carolina, 27534

  • Altru Cancer Center at Altru Hospital

    Grand Forks, North Dakota, 58201

  • Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center

    Grand Island, Nebraska, 68803

  • St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center

    Grand Junction, Colorado, 81502

  • Three Rivers Community Hospital

    Grants Pass, Oregon, 97527

  • Great Falls Clinic - Main Facility

    Great Falls, Montana, 59405

  • Sletten Cancer Institute at Benefis Healthcare

    Great Falls, Montana, 59405

  • Study site

    Great Falls, Montana, 59405

  • North Colorado Medical Center

    Greeley, Colorado, 80631

  • Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Marin Cancer Institute at Marin General Hospital

    Greenbrae, California, 94904

  • Moses Cone Regional Cancer Center at Wesley Long Community Hospital

    Greensboro, North Carolina, 27403-1198

  • Leo W. Jenkins Cancer Center at ECU Medical School

    Greenville, North Carolina, 27834

  • Wayne Hospital

    Greenville, Ohio, 45331

  • CCOP - Greenville

    Greenville, South Carolina, 29615

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • Van Elslander Cancer Center at St. John Hospital and Medical Center

    Grosse Pointe Woods, Michigan, 48236

  • CCOP - Northern New Jersey

    Hackensack, New Jersey, 07601

  • Virginia Oncology Associates - Hampton

    Hampton, Virginia, 23666

  • Helen and Harry Gray Cancer Center at Hartford Hospital

    Hartford, Connecticut, 06102-5037

  • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

    Hartford, Connecticut, 06105

  • Ingalls Cancer Care Center at Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Hattiesburg Clinic, PA at Forrest General

    Hattiesburg, Mississippi, 39401

  • Hematology & Oncology Clinic

    Hattiesburg, Mississippi, 39402

  • St. Peter's Hospital

    Helena, Montana, 59601

  • Maria Parham Medical Center

    Henderson, North Carolina, 27536

  • Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Memorial Cancer Institute at Memorial Regional Hospital

    Hollywood, Florida, 33021

  • New Hampshire Oncology - Hematology, PA - Hooksett

    Hooksett, New Hampshire, 03106

  • Edwards Comprehensive Cancer Center at Cabell Huntington Hospital

    Huntington, West Virginia, 25701

  • Hutchinson Area Health Care

    Hutchinson, Minnesota, 55350

  • Cape Cod Hospital

    Hyannis, Massachusetts, 02601

  • Cancer Center of Kansas-Independence

    Independence, Kansas, 67301

  • Holden Comprehensive Cancer Center at University of Iowa

    Iowa City, Iowa, 52242-1002

  • Foote Memorial Hospital

    Jackson, Michigan, 49201

  • University of Mississippi Cancer Clinic

    Jackson, Mississippi, 39216

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

  • Queens Cancer Center of Queens Hospital

    Jamaica, New York, 11432

  • Mercy Regional Cancer Center

    Janesville, Wisconsin, 53547

  • UW Cancer Center Johnson Creek

    Johnson Creek, Wisconsin, 53038

  • Midwest Center for Hematology/Oncology

    Joliet, Illinois, 60432

  • Joliet Oncology-Hematology Associates, Limited - West

    Joliet, Illinois, 60435

  • St. John's Regional Medical Center

    Joplin, Missouri, 64804

  • Ella Milbank Foshay Cancer Center at Jupiter Medical Center

    Jupiter, Florida, 33458

  • Borgess Medical Center

    Kalamazoo, Michigan, 49001

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007-3731

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Glacier Oncology, PLLC

    Kalispell, Montana, 59901

  • Kalispell Medical Oncology at KRMC

    Kalispell, Montana, 59901

  • Provena St. Mary's Regional Cancer Center - Kankakee

    Kankakee, Illinois, 60901

  • Truman Medical Center - Hospital Hill

    Kansas City, Missouri, 64108

  • Saint Luke's Cancer Institute at Saint Luke's Hospital

    Kansas City, Missouri, 64111

  • St. Joseph Medical Center

    Kansas City, Missouri, 64114

  • North Kansas City Hospital

    Kansas City, Missouri, 64116

  • Parvin Radiation Oncology

    Kansas City, Missouri, 64116

  • Heartland Hematology Oncology Associates, Incorporated

    Kansas City, Missouri, 64118

  • CCOP - Kansas City

    Kansas City, Missouri, 64131

  • Research Medical Center

    Kansas City, Missouri, 64132

  • Good Samaritan Cancer Center at Good Samaritan Hospital

    Kearney, Nebraska, 68848-1990

  • Kingsbury Center for Cancer Care at Cheshire Medical Center

    Keene, New Hampshire, 03431

  • Columbia Basin Hematology

    Kennewick, Washington, 99336

  • Charles F. Kettering Memorial Hospital

    Kettering, Ohio, 45429

  • Cancer Center of Kansas, PA - Kingman

    Kingman, Kansas, 67068

  • Kinston Medical Specialists

    Kinston, North Carolina, 28501

  • Cascade Cancer Center at Evergreen Hospital Medical Center

    Kirkland, Washington, 98033

  • Thompson Cancer Survival Center

    Knoxville, Tennessee, 37916

  • Howard Community Hospital

    Kokomo, Indiana, 46904

  • Franciscan Skemp Healthcare - La Crosse Campus

    La Crosse, Wisconsin, 54601

  • Gundersen Lutheran Center for Cancer and Blood

    La Crosse, Wisconsin, 54601

  • Rebecca and John Moores UCSD Cancer Center

    La Jolla, California, 92093-0658

  • Center for Cancer Therapy at LaPorte Hospital and Health Services

    La Porte, Indiana, 46350

  • Lakes Region General Hospital

    Laconia, New Hampshire, 03246

  • Center for Cancer Care and Research at Watson Clinic, LLP

    Lakeland, Florida, 33805

  • Lakeland Regional Cancer Center at Lakeland Regional Medical Center

    Lakeland, Florida, 33805

  • Haematology-Oncology Associates of Ohio and Michigan, PC

    Lambertville, Michigan, 48144

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17604

  • Sparrow Regional Cancer Center

    Lansing, Michigan, 48912-1811

  • University Medical Center of Southern Nevada

    Las Vegas, Nevada, 89102

  • CCOP - Nevada Cancer Research Foundation

    Las Vegas, Nevada, 89106

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • Cleo Craig Cancer Research Clinic

    Lawton, Oklahoma, 73505

  • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0002

  • Tunnell Cancer Center at Beebe Medical Center

    Lewes, Delaware, 19958

  • Lewistown Hospital

    Lewistown, Pennsylvania, 17044

  • Southwest Medical Center

    Liberal, Kansas, 67901

  • St. Rita's Medical Center

    Lima, Ohio, 45801

  • Lima Memorial Hospital

    Lima, Ohio, 45804

  • Cancer Resource Center - Lincoln

    Lincoln, Nebraska, 68510

  • St. Mary Mercy Hospital

    Livonia, Michigan, 48154

  • Dana-Farber Cancer Institute at Londonderry

    Londonderry, New Hampshire, 03053

  • Sky Ridge Medical Center

    Lone Tree, Colorado, 80124

  • Hope Cancer Care Center at Longmont United Hospital

    Longmont, Colorado, 80501

  • USC/Norris Comprehensive Cancer Center and Hospital

    Los Angeles, California, 90089-9181

  • McKee Medical Center

    Loveland, Colorado, 80539

  • Lowell General Hospital

    Lowell, Massachusetts, 01854

  • Southeastern Regional Medical Center

    Lumberton, North Carolina, 28359

  • Lynchburg Hematology-Oncology Clinic

    Lynchburg, Virginia, 24501

  • Medical Center of Central Georgia

    Macon, Georgia, 31208

  • Dean Medical Center - Madison

    Madison, Wisconsin, 53717

  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

    Madison, Wisconsin, 53792-6164

  • Elliot Regional Cancer Center at Elliot Hospital

    Manchester, New Hampshire, 03103

  • Holy Family Memorial Medical Center Cancer Care Center

    Manitowoc, Wisconsin, 54221-1450

  • Immanuel St. Joseph's

    Mankato, Minnesota, 56002

  • HealthEast Cancer Care at St. John's Hospital

    Maplewood, Minnesota, 55109

  • Minnesota Oncology Hematology, PA - Maplewood

    Maplewood, Minnesota, 55109

  • Strecker Cancer Center at Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Vince Lombardi Cancer Clinic - Marinette

    Marinette, Wisconsin, 54143

  • Marshfield Clinic - Marshfield Center

    Marshfield, Wisconsin, 54449

  • Saint Joseph's Hospital

    Marshfield, Wisconsin, 54449

  • Contra Costa Regional Medical Center

    Martinez, California, 94553-3156

  • Tibotec Therapeutics - Division of Ortho Biotech Products, LP

    Marysville, California, 95901

  • Northwest Ohio Oncology Center

    Maumee, Ohio, 43537-1839

  • St. Luke's Hospital

    Maumee, Ohio, 43537

  • Cardinal Bernardin Cancer Center at Loyola University Medical Center

    Maywood, Illinois, 60153

  • Dubs Cancer Center at Rogue Valley Medical Center

    Medford, Oregon, 97504

  • Providence Cancer Center at PMCC

    Medford, Oregon, 97504

  • Columbia Saint Mary's Hospital - Ozaukee

    Mequon, Wisconsin, 53097

  • CCOP - Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Saint Anthony Memorial Health Centers

    Michigan City, Indiana, 46360

  • Aurora Sinai Medical Center

    Milwaukee, Wisconsin, 53201-0342

  • Columbia-Saint Mary's Cancer Care Center

    Milwaukee, Wisconsin, 53211

  • Medical Consultants, Limited

    Milwaukee, Wisconsin, 53215

  • Providence Milwaukie Hospital

    Milwaukie, Oregon, 97222

  • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center - Minneapolis

    Minneapolis, Minnesota, 55415

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • Marshfield Clinic - Lakeland Center

    Minocqua, Wisconsin, 54548

  • Trinity CancerCare Center

    Minot, North Dakota, 58701

  • Community Medical Center

    Missoula, Montana, 59801

Other trials in United States

South Africa1 site

  • Pretoria Academic Hospital

    Pretoria, 0002

Other trials in South Africa

About this study

Official title: Cyclophosphamide And Doxorubicin (CA) (4 VS 6 Cycles) Versus Paclitaxel (4 VS 6 Cycles) As Adjuvant Therapy For Breast Cancer in Women With 0-3 Positive Axillary Lymph Nodes:A 2X2 Factorial Phase III Randomized Study

This randomized phase III trial studies cyclophosphamide and doxorubicin hydrochloride compared with paclitaxel as adjuvant therapy in treating breast cancer in women with 0-3 positive axillary lymph nodes. Giving additional cancer treatment after surgery may help to lower the risk that the cancer will come back (adjuvant therapy). Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether the standard adjuvant therapy of cyclophosphamide and doxorubicin hydrochloride is more effective than paclitaxel in treating women with breast cancer

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the equivalence of paclitaxel given every two weeks with cyclophosphamide and doxorubicin hydrochloride (CA) given every two weeks as adjuvant therapy for women with 0-3 positive axillary lymph nodes, for disease-free survival.

II. To determine if longer therapy, 12 weeks, is superior to shorter therapy, 8 weeks, of either CA or paclitaxel for disease-free survival for women with primary breast cancer with 0-3 positive axillary lymph nodes.

SECONDARY OBJECTIVES:

  1. To determine the equivalence of paclitaxel given every two weeks with CA given every two weeks, and the potential superiority of longer vs. shorter therapy, in relation to overall survival, local control (regardless of metastatic status) and time to distant metastases (regardless of local recurrence status).

II. To compare toxicities of short and long course CA and paclitaxel as adjuvant therapy for women with 0-3 positive axillary lymph node breast cancer.

III. To determine the effect of long and short course CA and paclitaxel on the induction of menopause for pre-menopausal patients.

IV. To assess the discrepancy of myelosuppression among the common multidrug resistance protein 1 (MDR1) haplotypes in the CA treatment arm.

  1. To assess the effect of MDR1 haplotypes on disease-free survival (DFS) adjusted for treatment.

VI. Exploratory analysis of the effect of cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5), cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8), and cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6) polymorphisms on DFS and toxicity.

VII. To identify genetic markers associated with the risk of developing neutropenia in adriamycin/ cyclophosphamide-treated breast cancer patients.

VIII. To identify genetic markers associated with the risk of developing peripheral neuropathy in paclitaxel-treated breast cancer patients.

IX. To identify genetic markers associated with differences in the efficacy of each chemotherapy regimen.

  1. To examine genetic associations with other response and toxicity phenotypes that become apparent during future analysis of Cancer and Leukemia Group B (CALGB) 40101 data.

XI. To identify copy number variants associated with adriamycin/cyclophosphamide-induced neutropenia and paclitaxel-induced peripheral neuropathy.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive cyclophosphamide intravenously (IV) and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM IV: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Note: Randomization to Arms II and IV is no longer available, effective 12/15/2007.

After completion of study treatment patients are followed up for 4-6 weeks, every 6 months for 2 years, and then annually for up to 13 years.

Conditions
Breast Cancer
Keywords
stage IB breast cancer, stage II breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00041119
Study groupRoleWhat they receive
Arm I (CA for 4 courses)Active comparatorPatients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: AC regimen; Drug: doxorubicin hydrochloride
Arm II (CA for 6 courses [closed to accrual 12/15/2007])ExperimentalPatients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: AC regimen; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride
Arm III (paclitaxel for 4 courses)ExperimentalPatients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: AC regimen; Drug: paclitaxel
Arm IV (paclitaxel for 6 courses [closed 12/15/2007])ExperimentalPatients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: AC regimen; Drug: paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Relapse Free Survival (RFS) 4 vs. 6 Cycles

    To determine if longer therapy, 12 weeks, is superior to shorter therapy, 8 weeks, of either CA or paclitaxel for relapse-free survival for women with primary breast cancer with 0-3 positive axillary lymph nodes. An assessment of the superiority of 6 cycles over 4 cycles will be conducted. This analysis combines Arm I and Arm III together, and Arm II and Arm IV together.

    Measured: from baseline up to 4 years

  2. Duration of Disease Free Survival (RFS)

    To determine the equivalence of paclitaxel to CA as adjuvant therapy for women with 0-3 positive axillary lymph nodes, for disease-free survival. Objective progression is defined as the appearance of local (chest wall, axillary, supraclavicular nodes) or distant metastases. The trial is designed to show the equivalence of the experimental agent T with the standard agent combination CA, thus the 4 and 6 course arms of each drug will be combined to conduct this analysis.

    Measured: from baseline up to 6.4 years

Secondary outcomes (5)

  1. Overall Survival (OS)

    To determine the equivalence of paclitaxel to CA as adjuvant therapy for women with 0-3 positive axillary lymph nodes, for overall survival. OS will be measured from study entry until death due to any cause. Survivors will be censored at the date of last follow-up.. The trial is designed to show the equivalence of the experimental agent T with the standard agent combination CA, thus the 4 and 6 course arms of each drug will be combined to conduct this analysis.

    Measured: from baseline up to 5 years

  2. Adverse Events

    To compare toxicities of short course CA and paclitaxel with long course CA and paclitaxel as adjuvant therapy for women with 0-3 positive axillary lymph node breast cancer. The percentage of patients that received a grade 3 or higher hematologic event will be reported here. We will be combining arm I with arm III, as well as arm II with arm IV. For a complete list of adverse events, please refer to the adverse events section.

    Measured: from baseline up to 6 weeks post-treatment

  3. Time to Distant Metastases

    Local control and distant metastasis will be calculated as the cumulative incidence of first local relapse and first distant metastasis, respectively.

    Measured: from baseline up to 15 years

  4. Local Control

    Local control will be calculated as the cumulative incidence of first local relapse.

    Measured: from baseline up to 15 years

  5. Overall Survival (OS) for 4 vs. 6 Cycles

    To determine if longer therapy, 12 weeks, is superior to shorter therapy, 8 weeks, of either CA or paclitaxel for overall survival for women with primary breast cancer with 0-3 positive axillary lymph nodes. An assessment of the superiority of 6 cycles over 4 cycles will be conducted. This analysis combines Arm I and Arm III together, and Arm II and Arm IV together.

    Measured: from baseline up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startMay 2002
  3. Primary completionApr 2012
  4. Study completionJun 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
3,871 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00041119
Sponsor's protocol ID
CALGB-40101
Other IDs
CDR0000069444, NCI-2009-00474, U10CA180821
Status last verified
Apr 2017
First submitted
8 Jul 2002
Last updated
18 May 2017
Data monitoring committee
Yes

Publications

  • Baldwin RM, Owzar K, Zembutsu H, Chhibber A, Kubo M, Jiang C, Watson D, Eclov RJ, Mefford J, McLeod HL, Friedman PN, Hudis CA, Winer EP, Jorgenson EM, Witte JS, Shulman LN, Nakamura Y, Ratain MJ, Kroetz DL. A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. Clin Cancer Res. 2012 Sep 15;18(18):5099-109. doi: 10.1158/1078-0432.CCR-12-1590. Epub 2012 Jul 27.

    PubMed 22843789

  • Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or Paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. doi: 10.1200/JCO.2011.40.6405. Epub 2012 Jul 23.

    PubMed 22826271

  • Barginear M, Dueck AC, Allred JB, Bunnell C, Cohen HJ, Freedman RA, Hurria A, Kimmick G, Le-Rademacher JG, Lichtman S, Muss HB, Shulman LN, Copur MS, Biggs D, Ramaswamy B, Lafky JM, Jatoi A. Age and the Risk of Paclitaxel-Induced Neuropathy in Women with Early-Stage Breast Cancer (Alliance A151411): Results from 1,881 Patients from Cancer and Leukemia Group B (CALGB) 40101. Oncologist. 2019 May;24(5):617-623. doi: 10.1634/theoncologist.2018-0298. Epub 2018 Nov 8.

    PubMed 30409792

  • Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. doi: 10.1200/JCO.2013.53.7142. Epub 2014 Jun 16.

    PubMed 24934787

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AC regimen, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by Alliance for Clinical Trials in Oncology at 527 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 527 sites in United States, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relapse Free Survival (RFS) 4 vs. 6 Cycles (time frame: from baseline up to 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00041119, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2017.

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